The purpose of this study is to delineate the molecular anatomy of mitochondrial genetic changes in head and neck cancer development. Mitochondrial mutations and genetic alterations have been found in head and neck cancer and mitochondrial dysfunction, DNA damage, and apoptotic dysregulation are found in multiple solid tumors. The entire 16 KB mitochondrial genome will be tested using conventional PCR based and novel array based sequencing assays in primary head and neck cancers and premalignant lesions. These alterations will be placed in the context of a genetic progression model for head and neck cancer to determine mitochondrial alterations that occur early in progression. Identified or engineered mutations in cell lines will be tested to understand their impact on mitochondrial biology and their role in cancer progression. Ultimately, identified mitochondrial alterations will be used as markers for molecular detection approaches using a novel, fluorescence based gap ligase chain reaction assay. [unreadable] [unreadable]